Shear waves in viscoelastic wormlike micellar fluids over a broad concentration range.

Low frequency (61 Hz) shear wave speeds have been measured in viscoelastic wormlike micellar (WM) fluids for a concentration range of 20/12-500/300 mM CTAB/NaSAL where CTAB is the surfactant and NaSAL is the salt and the concentration ratio was fixed at 0.6 for all experiments. The birefringent property of the WM fluids was exploited to visually track the the shear pulse using crossed optical polarizing filters and high speed video. Several scalings of shear wave speed as a function of concentration were discovered: c(s) ~ √C for 20-200 mM and c(s) ~ C for higher concentrations, but with a break in the slope at 400 mM CTAB. Over this full concentration range, the shear wave speed varied from 0.08-0.7 m/s. The shear wave speed was also found to be sensitive to the time between fluid synthesis and measurement indicating a long equilibrium time. Further, comparison with elastic and loss moduli obtained from rheology data show that shear wave propagation is dominated by the elastic modulus for this frequency range. Also briefly discussed are potential applications of this fluid in elastography.

Shear waves in viscoelastic wormlike micellar fluids.

Low frequency (61 Hz) shear wave speeds have been measured in viscoelastic wormlike micellar (WM) fluids for a concentration range of 20/12-160/96 mM CTAB/NaSAL. The strain induced birefringence of the WM fluids was exploited to optically track the shear pulse using crossed polarizing filters and high speed video. It was found that shear speed increases roughly linearly with concentration at a rate of 3.5 mm s(-1) mM(-1) CTAB. Further, comparison with elastic and loss moduli obtained from rheology data show that shear wave propagation is dominated by the elastic modulus for this frequency range.

A role for phosphatidylinositol 3-kinase in the regulation of beta 1 integrin activity by the CD2 antigen.

The rapid and reversible upregulation of the functional activity of integrin receptors on T lymphocytes is a vital step in the adhesive interactions that occur during successful T cell recognition of foreign antigen and transendothelial migration. Although the ligation of several different cell surface receptors, including the antigen-specific CD3/T cell receptor complex, the CD2, CD7, and CD28 antigens, as well as several chemokine receptors, has been shown to rapidly upregulate integrin function, the intracellular signaling events that initiate this increase in adhesion remain poorly defined. In this study, we have used DNA-mediated gene transfer to explore the role of phosphatidylinositol 3-kinase (PI 3-K) in the upregulation of beta 1 integrin functional activity mediated by the CD2 antigen. CD2 was expressed in the myelomonocytic cell line HL60, which expresses beta 1 integrins that mediate adhesion to fibronectin and VCAM-1 in an activation-dependent manner. Antibody stimulation of CD2 expressed on HL60 transfectants resulted within minutes in increased beta 1-mediated adhesion to fibronectin and VCAM-1 at levels comparable to that obtained upon stimulation with the phorbol ester PMA. A role for PI 3-K in CD2-mediated increases in beta 1 integrin function is suggested by: (a) the ability of the PI 3-K inhibitor wortmannin to completely inhibit CD2-induced increases in beta 1 integrin activity; (b) the association of PI 3-K with CD2; and (c) induced PI 3-K activity upon CD2 stimulation. The mode of association of PI 3-K with CD2 is not mediated by tyrosine phosphorylation-dependent binding of PI 3-K via SH2 domains, since: (a) PI 3-K is associated with CD2 in unstimulated cells; (b) CD2 stimulation fails to increase the amount of associated PI 3-K; and (c) the CD2 cytoplasmic domain lacks tyrosine residues. A role for both protein kinase C and cytoskeletal rearrangements in CD2 regulation of integrin activity is also suggested, since a PKC inhibitor partially inhibits CD2-induced increases in beta 1 integrin function, and CD2 stimulation increases F-actin content in a wortmannin-sensitive manner. Analysis of human peripheral T cells indicated that CD2 stimulation also results in PI 3-K-dependent upregulation of beta 1 integrin activity. Thus, these results demonstrate that CD2 can function as an adhesion regulator in the absence of expression of the CD3/T cell receptor complex; and directly implicate PI 3-K as a critical intracellular mediator involved in the regulation of beta 1 integrin functional activity by the CD2 antigen.

Identification of a proline-rich sequence in the CD2 cytoplasmic domain critical for regulation of integrin-mediated adhesion and activation of phosphoinositide 3-kinase.

The CD2 molecule is one of several lymphocyte receptors that rapidly initiates signaling events regulating integrin-mediated cell adhesion. CD2 stimulation of resting human T cells results within minutes in an increase in beta1-integrin-mediated adhesion to fibronectin. We have utilized the HL60 cell line to map critical residues within the CD2 cytoplasmic domain involved in CD2 regulation of integrin function. A panel of CD2 cytoplasmic domain mutants was constructed and analyzed for their ability to upregulate integrin-mediated adhesion to fibronectin. Mutations in the CD2 cytoplasmic domain implicated in CD2-mediated interleukin-2 production or CD2 avidity do not affect CD2 regulation of integrin activity. A proline-rich sequence, K-G-P-P-L-P (amino acids 299 to 305), is essential for CD2-mediated regulation of beta1 integrin activity. CD2-induced increases in beta1 integrin activity could be blocked by two phosphoinositide 3-kinase (PI 3-K) inhibitors or by overexpression of a dominant negative form of the p85 subunit of PI 3-K. In addition, CD2 cytoplasmic domain mutations that abrogate CD2-induced increases in integrin-mediated adhesion also ablate CD2-induced increases in PI 3-K enzymatic activity. Surprisingly, CD2 cytoplasmic domain mutations that inhibit CD2 regulation of adhesion do not affect the constitutive association of the p85 subunit of PI 3-K association with CD2. Mutation of the proline residues in the K-G-P-P-L-P motif to alanines prevented CD2-mediated activation of integrin function and PI 3-K activity but not mitogen-activated protein (MAP) kinase activity. Furthermore, the MEK inhibitor PD 098059 blocked CD2-mediated activation of MAP kinase but had no effect on CD2-induced adhesion. These studies identify a proline-rich sequence in CD2 critical for PI 3-K-dependent regulation of beta1 integrin adhesion by CD2. In addition, these studies suggest that CD2-mediated activation of MAP kinase is not involved in CD2 regulation of integrin adhesion.

Air emission inventories in North America: a critical assessment.

Although emission inventories are the foundation of air quality management and have supported substantial improvements in North American air quality, they have a number of shortcomings that can potentially lead to ineffective air quality management strategies. Major reductions in the largest emissions sources have made accurate inventories of previously minor sources much more important to the understanding and improvement of local air quality. Changes in manufacturing processes, industry types, vehicle technologies, and metropolitan infrastructure are occurring at an increasingly rapid pace, emphasizing the importance of inventories that reflect current conditions. New technologies for measuring source emissions and ambient pollutant concentrations, both at the point of emissions and from remote platforms, are providing novel approaches to collecting data for inventory developers. Advances in information technologies are allowing data to be shared more quickly, more easily, and processed and compared in novel ways that can speed the development of emission inventories. Approaches to improving quantitative measures of inventory uncertainty allow air quality management decisions to take into account the uncertainties associated with emissions estimates, providing more accurate projections of how well alternative strategies may work. This paper discusses applications of these technologies and techniques to improve the accuracy, timeliness, and completeness of emission inventories across North America and outlines a series of eight recommendations aimed at inventory developers and air quality management decision-makers to improve emission inventories and enable them to support effective air quality management decisions for the foreseeable future.

Virological and immunological responses to once-daily dosing of didanosine in combination with stavudine. AI454-143 Team.

OBJECTIVE: To compare the antiviral activity of once-daily didanosine (ddI) and twice-daily ddI in combination with stavudine (d4T). DESIGN: Randomized, double-blind, multicenter study. SETTING: Twenty-one sites in the United States. PATIENTS: Eighty-seven antiretroviral-naive, HIV-1-infected adults with baseline plasma HIV RNA counts of > or = 10,000 copies/ml and CD4 cell counts of > or = 100 cells/mm3 started study therapy. INTERVENTIONS: Patients received once-daily ddI or twice-daily ddI, each combined with twice-daily d4T. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA levels, CD4 cell counts, and adverse events were regularly monitored. The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens in change from baseline plasma HIV-1 RNA levels over the first 12 weeks of therapy. RESULTS: At week 12, median log10 HIV-1 RNA changes were -1.83 log10 copies/ml in the once-daily ddI/d4T group and -1.80 log10 copies/ml in the twice-daily ddI/d4T group, and 18 out of 44 patients (41%) and 17 out of 43 patients (40%), respectively, had HIV-1 RNA levels below 400 copies/ml. Similar results were seen at week 24. The TAD between the two treatment groups (once-daily ddI/d4T minus twice-daily ddI/d4T) in change from baseline plasma HIV RNA levels over the first 12 weeks was 0.14 log10 copies/ml (95% CI: -0.11, 0.40). At week 12, subjects averaged an increase in CD4 cell count of over 140 cells/mm3. The TAD between the two treatment groups in change from baseline CD4 cell counts over the first 12 weeks was 2 cells/mm3 (95% CI: -40, 45). CONCLUSION: Once-daily ddI plus d4T and twice-daily ddI plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy.

Effects of phytoestrogens and synthetic combinatorial libraries on aromatase, estrogen biosynthesis, and metabolism.

Approximately 60% of breast cancer patients have hormone-dependent breast cancer containing estrogen receptors and requiring estrogen for tumor growth. The extent of estrogen biosynthesis and metabolism in the breast cancer tissue microenvironment influences breast-tumor development and growth, and endogenous and exogenous agents may alter the levels of hormonally active estrogens and their metabolites. Isoflavonoid phytoestrogens such as genistein exhibit numerous biochemical activities; however, their effects on estrogen biosynthesis and metabolism in breast cancer cells have not been fully examined. MCF-7 cells (hormone-dependent) and MBA-MB-231 cells (hormone-independent) were treated with genistein (100 nM) for five days and then incubated with radiolabeled estradiol (100 nM, 2.5 microCi) for 0 to 48 h. Media were extracted with ethyl acetate, and the organic residues analyzed by reverse-phase HPLC with a radioactivity flow detector. The major metabolite formed in all cases is estrone, although differences were observed between the cell lines and the various drug treatments. The formation of estrone in untreated MCF-7 cells (approximately 9.3% of radioactivity at 24 h) is relatively limited, in contrast to untreated MDA-MB-231 cells (approximately 32.0% of radioactivity at 24 h). Treatment of MCF-7 cells with 100 nM genistein increased the conversion of estradiol to estrone up to 19.5% in 24 h. The effect of genistein on estrone formation in MDA-MB-231 cells resulted in 37.7% of the radioactivity being estrone. Thus, genistein treatment of breast cancer cells resulted in increased 17-betahydroxysteroid dehydrogenase activity and elevated formation of estrone. Increased levels of oxidative 17-betahydroxysteroid dehydrogenase activity (Type II) were confirmed by Western blots. Therefore, exposure of breast cancer cells to genistein results in elevated conversion of estradiol to estrogenically weaker or inactive metabolites. The regulation of breast-tissue aromatase by exogenous agents such as drugs and environmental agents is being investigated. The benzopyranone-ring system is a molecular scaffold of considerable interest, and this scaffold is found in flavonoid natural products that have weak aromatase inhibitory activity. Medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aro- matase inhibitors. Several compounds in the initial libraries have demonstrated moderate aromatase inhibitory activity in screening assays.

Nephrogenic adenoma.

Nephrogenic adenoma is an uncommon, benign, apparently metaplastic response of urothelium to chronic infection or irritation. Endoscopically, these lesions easily can be mistaken for malignant tumors, and their scarcity only heightens the possibility of this error. A case report of nephrogenic adenoma accompanied by endoscopic photographs is presented to improve awareness and avoid inappropriate therapy.

Cyclic variation of integrated backscatter: dependence of time delay on the echocardiographic view used and the myocardial segment analyzed.

To determine the influence of myocardial anisotropy in ultrasonic tissue characterization, we measured the time delay (and magnitude) of the cyclic variation of myocardial integrated backscatter from specific segments visualized in the 4 standard transthoracic echocardiographic views. The cyclic variation data in 10 myocardial regions were obtained from analyses of 2-dimensional integrated backscatter images from 23 healthy subjects. Resultant values (mean +/- SD) for the time delay were as follows: parasternal long-axis view: 1.08 +/- 0.17 (septum) and 1.00 +/- 0.14 (posterior wall); parasternal short-axis view: 1.03 +/- 0.16 (anterior septum), 1.03 +/- 0.14 (posterior wall), 2.22 +/- 0.71 (lateral wall), and 1.65 +/- 0.66 (posterior septum); apical 4-chamber view: 1.08 +/- 0.31 (septum) and 2.20 +/- 0.79 (lateral wall); and apical 2-chamber view: 1.68 +/- 0.62 (inferior wall) and 2.04 +/- 0.72 (anterior wall). Hence, results of this study indicate that myocardial ultrasonic characterization that uses the cyclic variation is influenced by the echocardiographic view and the specific segment of the left ventricle.

Antibody-based biosensor for breast cancer with ultrasonic regeneration.

We describe a novel method and instrumental setup for regenerating antibodies immobilized on a fiberoptic probe of an immunosensor using ultrasonic irradiation with broadband imaging transducers. The instrumental setup and irradiation conditions for antibody regeneration using ultrasound are described. The results of the measurements with antibody against breast cancer antigen illustrate the effectiveness and potential of the regenerable immunosensor. A 65% removal of the antigens bound to the Mab immobilized on the fiber surface is attained after ultrasound regeneration.

Dependence of "apparent" magnitude on the time delay of cyclic variation of myocardial backscatter.

The goal of this study was to determine if the "apparent" magnitude of the cyclic variation, defined as the difference between the values of integrated backscatter at end-diastole and end-systole, was dependent on the corresponding time delay. We measured the cyclic variation in four myocardial segments of the parasternal short-axis view in 23 healthy subjects. The "apparent" magnitude, actual magnitude, and time delay were compared for each segment. Measured time delays were: 2.22+/-0.71 (lateral wall); 1.65+/-0.66 (inferior septum); and approximately 1.0 for the anterior septum and posterior wall. Segments exhibiting large time delays (> 1.0) resulted in a reversal in sign of the "apparent" magnitude of cyclic variation in one instance, and underestimated the true magnitude in both cases. Thus, estimates of the "apparent" magnitude of the cyclic variation are dependent on the associated time delay, whereas a properly defined magnitude is not.

Risk factors for secondary arrest of labor among women >41 weeks' gestation with an unfavorable cervix undergoing membrane sweeping for cervical ripening.

OBJECTIVE: To identify the risk factor(s) for secondary arrest of labor among women with an unfavorable cervix at > 41 weeks' gestation. METHODS: Prospectively all gravid women with a Bishop score of < or = 4 and no contraindication to a vaginal delivery were candidates for this study. Univariate analysis followed by logistic regression modeling were used to identify variables with a significant association. RESULTS: Over a 9-month period, 115 women entered into the study. In univariate analysis, variables with a significant association with cesarean delivery: (1) non-Caucasian race (P = 0.007), Bishop score < 7 at hospitalization; P = 0.001, and reason for admission (P = 0.017). Logistic regression analysis yielded OR 4.7 (1.6, 15) non-Caucasian race and 9.5 (3.2, 30.8) Bishop < 7 on admission. CONCLUSION: Pregnancies > 41 weeks with an unfavorable cervix, non-Caucasian race and a failure to achieve a Bishop score of > or = 7 prior to hospitalization were significant risk factors for abdominal delivery.

Risk factors associated with blood transfusion in ectopic pregnancy.

OBJECTIVE: To determine the risk factors associated with blood transfusion in ectopic pregnancy. STUDY DESIGN: A retrospective chart review of the presentation and hospital course of ectopic pregnancies managed over five years at two hospitals was undertaken. Thirty-two variables, including demographics, presenting signs and symptoms, and intraoperative findings, were examined with univariate and multivariate logistic modeling. RESULTS: Among 185 patients with histologically confirmed ectopics who were managed surgically, 8.6% (16 women) required transfusion. Multivariate analysis of risk factors for blood transfusion demonstrated a statistically significant association with (1) initial hemoglobin < 10 g/dL (odds ratio [OR] 38.8, 95% confidence interval [CI] 6.0-356.8); (2) human chorionic gonadotropin levels > or = 6,500 mIU (OR 18.1, 95% CI 3.6-158.1); and (3) abnormal bleeding on presentation (OR 0.08, 95% CI 0.007-0.42). The presence of two of these factors had a sensitivity of 82% (95% CI 48-98%) and a positive predictive value of 33% (95% CI 16-54%). No case had all three factors. CONCLUSION: This study was, to our knowledge, the first regression analysis of risk factors for transfusion associated with ectopic pregnancy. It demonstrated that initial hemoglobin and human chorionic gonadotropin levels as well as abnormal bleeding on presentation are independent risk factors for blood transfusion in ectopic pregnancy.

Cesarean delivery for suspected fetal distress among preterm parturients.

OBJECTIVE: Among preterm parturients (< 37 weeks) who underwent cesarean delivery for suspected fetal distress, to determine the factors associated with decision-incision time (DIT) of < or = 30 minutes and to assess if umbilical arterial pH < 7.10 is more common with DIT < or = 30 or > 30 minutes. STUDY DESIGN: The peripartum course of all patients who had cesareans for suspected fetal distress over three years was reviewed. The inclusion criteria were reliable gestational age < 37 weeks and a single indication for cesarean delivery, suspected fetal distress. Twenty antepartum and intrapartum factors were used in a univariate analysis. RESULTS: The mean DIT among the 84 parturients was 30.5 +/- 21.2 minutes, and 63% of patients had surgery started within 30 minutes. The incidence of pH < 7.10 was 20%. Multivariate analysis indicated that the two factors significantly associated with prolonged time to surgery were tachycardia with decreased variability (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.6-21.6) and use of spinal anesthesia (OR 6.2, 95% CI 1.1-35.0). Though none of the 20 variables had significant univariate associations with neonatal acidosis at alpha = .05, those with P < .20 were considered in multiple logistic regression analysis. None of the 20 factors were associated with pH < 7.10, including DIT of > or = 30 minutes (OR 0.26, 95% CI 0.06-1.03). CONCLUSION: DIT is likely to be > 30 minutes if cesarean delivery is due to decreased fetal heart variability or if spinal anesthesia is utilized; neonatal acidosis, however, is not significantly associated with a prolonged interval.

Unengaged vertex in nulliparous women in active labor. A risk factor for cesarean delivery.

OBJECTIVE: To compare the route of delivery among nulliparous parturients with and without an engaged vertex in the early, active phase of labor. METHODS: Prospectively, the position of the fetal head was ascertained among nulliparous women at 37 weeks' gestation or more in early, active labor (cervical dilation > or = 4 cm with adequate contractions). Sixteen variables, including maternal demographics, obstetric complications and intrapartum course, were examined using chi 2 and logistic regression analysis. RESULTS: Among the 77 patients, 33 (42.8%) had an unengaged vertex and 44 (57.2%) had an engaged vertex in active labor. Of the 22 cesarean deliveries for arrest disorder, 2 were in the engaged and 20 in the unengaged group (P < .001). The mean birth weight was similar among those who had vaginal (3,211 +/- 416 g) and cesarean delivery (3,400 +/- 489 g, P = .08). Univariate analysis indicated that chorioamnionitis (relative risk [RR] 2.6, 95% confidence interval [CI] 1.4-4.9) and unengaged vertex (RR 13.3, CI 3.3-53.0) were associated with cesarean delivery for arrest disorders. When entered into a multiple logistic model, only unengagement was a risk factor for cesarean delivery. The following were not associated with cesarean delivery: maternal demographics, gestational age, estimate of fetal weight, presence or absence of meconium, preeclampsia, diabetes mellitus, private obstetric care or use of epidural anesthesia. CONCLUSION: Among nulliparous parturients, an unengaged vertex is a significant risk factor for cesarean delivery for arrest disorders.

Emergency room management of minor burn injuries: a quality management evaluation.

The vast majority of acute burns are initially seen and treated in emergency departments (EDs). Most of the individuals caring for these patients have little or no specialized training in the multidisciplinary approach to the burned patient. Burns of limited severity are treated immediately and then followed on an outpatient basis; therefore reviews of documented practices in emergency departments were not found. It was hypothesized that follow-up care may be suboptimal in this population. The medical records of 791 patients treated at three EDs in a Midwestern regional referral area from January 1991 through December 1991 were evaluated to assess the documentation of care provided. The three hospitals included a tertiary care teaching facility, a pediatric facility, and a community-based teaching hospital. Only the charts of patients treated and released from the ED were evaluated. The data demonstrate that there was suboptimal documentation of diagnosis, treatment, and follow-up care of the thermally injured patients who were initially treated in these EDs. Burn team members should develop educational and clinical relationships with EDs in the referral area to optimize both the delivery and documentation of outpatient burn care. This is especially important in today's health care environment, in which reimbursement is based on services rendered.

Electrical stimulation of the auditory brain stem structure in deafened adults.

Electrical stimulation of the cochlear nuclear complex in the brain stem was first accomplished in a female adult deafened by bilateral acoustic tumors. The central electroauditory prosthesis (CEP) was surgically placed at the time of the second tumor removal. The patient has now been receiving electrical stimulation for 5 years. Six more adults have received the CEP at the time of tumor surgery. Clinical results indicate fluctuations in electrical measurements over time, particularly in the first weeks following surgery. Patients are able to sustain tone perception for one minute at all frequencies tested. Auditory discrimination test results reveal above-chance performance on suprasegmental measures, similar to scores achieved by cochlear implant users. No serious complications have occurred to date.

On the applicability of Kramers-Kronig relations for ultrasonic attenuation obeying a frequency power law

In the recent literature concern has been raised regarding the validity of Kramers-Kronig relations for media with ultrasonic attenuation obeying a frequency power law. It is demonstrated, however, that the Kramers-Kronig dispersion relations for application to these types of media are available. The developed dispersion relations are compared with measurements on several liquids, and agreement is found to better than 1 m/s over the experimentally available bandwidth. A discussion regarding the validity of these dispersion relations, in particular how the dispersion relations relate to the so-called Paley-Wiener conditions, forms the conclusion.

Kramers-Kronig relations applied to finite bandwidth data from suspensions of encapsulated microbubbles

In this work, the Kramers-Kronig (K-K) relations are applied to experimental data of resonant nature by limiting the interval of integration to the measurement spectrum. The data are from suspensions of encapsulated microbubbles (Albunex) and have the characteristics of an ultrasonic notch filter. The goal is to test the consistency of this dispersion and attenuation data with the Kramers-Kronig relations in a strict manner, without any parameters from outside the experimental bandwidth entering in to the calculations. In the course of reaching the goal, the artifacts associated with the truncation of the integrals are identified and it is shown how their impacts on the results can be minimized. The problem is first approached analytically by performing the Kramers-Kronig calculations over a restricted spectral band on a specific Hilbert transform pair (Lorentzian curves). The resulting closed-form solutions illustrate the type of artifacts that can occur due to truncation and also show that accurate results can be achieved. Next, both twice-subtracted and lower-order Kramers-Kronig relations are applied directly to the attenuation and dispersion data from the encapsulated microbubbles. Only parameters from within the experimental attenuation coefficient and phase velocity data sets are used. The twice-subtracted K-K relations produced accurate estimates for both the attenuation coefficient and dispersion across all 12 data sets. Lower-order Kramers-Kronig relations also produced good results over the finite spectrum for most of the data. In 2 of the 12 cases, the twice-subtracted relations tracked the data markedly better than the lower-order predictions. These calculations demonstrate that truncation artifacts do not overwhelm the causal link between the phase velocity and the attenuation coefficient for finite bandwidth calculations. This work provides experimental evidence supporting the validity of the subtracted forms of the acoustic K-K relations between the phase velocity and attenuation coefficient.

Innovative methods for emission inventory development and evaluation: workshop summary.

Emission inventories are an essential tool for evaluating, managing, and regulating air pollution. Refinements and innovations in instruments that measure air pollutants, models that calculate emissions, and techniques for data management and uncertainty assessment are needed to enhance emission inventories. This workshop provided recommendations for improving emission factors, improving emission models, and reducing inventory uncertainty. Communication that increases cooperation between developers and users of inventories is essential. Emission inventories that incorporate these improvements will meet the challenges of the future.